Ameliorative effects of pentoxifylline on NOS induced by diabetes in rat kidney

Abstract

Objectives Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. The NO system has been implicated in the pathogenesis of DN. In this study, we aimed to evaluate the healing effect of pentoxifylline on NOS in STZ-induced diabetic rat's kidney. Material and methods In this study, 50 Wistar albino male rats were used. The rats were divided into five groups; Group C control; Group D only diabetes; Group D + PI and D + PII diabetes + pentoxifylline; Group P only pentoxifylline. Group DPI rats received just pentoxifylline from the beginning of the experiments. However, Group DPII rats received saline in the first month and 50 mg/kg/day of pentoxifylline for the following month. At the end of two months, NOS expressions in kidney tissue were assessed using qRT-PCR and immunohistochemistry analysis. Results At the end of the experiments, desquamation of the epithelial cells of the tubules, clear glycogen-filled distal tubules and increased number of apoptotic cells were seen in Group D. Diabetic rats' nNOS immunoreactivity had increased and eNOS and iNOS immunoreactivity had decreased; nNOS, iNOS and eNOS mRNA levels tended to decrease compared to the control group. PTX ameliorated eNOS, iNOS and nNOS protein levels and apoptotic cells, but did not affect mRNA levels. Conclusion In conclusion, PTX has a healing effect on this damage by affecting NOS expression. ARTICLE HISTORY

The effects of tadalafil and pentoxifylline on apoptosis and nitric oxide synthase in liver ischemia/reperfusion injury

“…[28] showed that 40 mg/kg of PTX reduced inflammatory cell infiltration, hemorrhage, and edema in lung IR injury. Sönmez and Dündar [29] reported that 50 mg/kg of PTX ameliorated eNOS, iNOS, and neuronal NOS protein levels and apoptotic cells in the rat kidney. The beneficial effects of PTX are believed to occur through various mechanisms such as inhibition of PDE, increased cAMP levels and downregulation of tumor necrosis factor‐alpha, IL‐1, IL‐6, IL‐12, transforming growth factor‐β, interferon‐γ, stellate cell activation, and procollagen‐I mRNA expression [30,31].…”

Are the Therapeutic Effects of Huangqi (Astragalus membranaceus) on Diabetic Nephropathy Correlated with Its Regulation of Macrophage iNOS Activity?

“…A study in a model of chronic DN for 40 weeks showed that iNOS-derived NO modulates glomerulosclerosis and tubulointerstitial fibrosis in chronic STZ nephropathy [ 66 ]. The drugs for treating DN such as pentoxifylline could exert therapeutic effects by increasing the expression of iNOS protein in the kidneys of a mouse model of STZ-induced DN [ 67 ].…”

An update on diabetic kidney disease, oxidative stress and antioxidant agents

“…The mechanism for relationship between vitamin D and diabetic kidney disease remains unclear however various animal studies have shown that knockout of the vitamin D receptor in diabetic mice is accompanying by severe albuminuria and glomerulosclerosis. Therefore, vitamin D might slow down diabetic kidney disease progression by delaying destruction of b-islet cells, enhancing insulin secretion, and consequently assisting in glucose metabolism (29,30). …”